BACKGROUND Metagenomic next-generation sequencing (mNGS) is emerging as a promising technique for pathogens detection. However, reports on the application of mNGS in mixed pulmonary infection remain scarce. METHODS From July 2018 to March 2019, 55 cases were enrolled in this retrospective analysis. Cases were classified into mixed pulmonary infection (36 [65.5%]) and non-mixed pulmonary infection (19 [34.5%]) according to primary diagnoses. The performances of mNGS and conventional test on mixed pulmonary infection diagnosis and pathogen identification were compared. RESULTS The sensitivity of mNGS in mixed pulmonary infection diagnosis was much higher than that of conventional test (97.2% vs 13.9%; P < 0.01), but the specificity was the opposite (63.2% vs 94.7%; P = 0.07). The positive predictive value of mNGS was 83.3% (95% CI, 68.0-92.5%), and the negative predictive value was 92.3% (95% CI, 62.1-99.6%). A total of 5 (9.1%) cases were identified as mixed pulmonary infection by both conventional tests and mNGS, however, the pathogens identification results were consistent between these two methods in only 1 (1.8%) case. In summary, the pathogens detected by mNGS in 3 (5.5%) cases were consistent with those by conventional test, and only 1 (1.8%) case was mixed pulmonary infection. According to our data, mNGS had a broader spectrum for pathogen detection than conventional tests. In particular, application of mNGS improved the diagnosis of pulmonary fungal infections. Within the 55 cases, mNGS detected and identified fungi in 31 (56.4%) cases, of which only 10 (18.2%) cases were positive for the same fungi by conventional test. The most common pathogen detected by mNGS was Human cytomegalovirus in our study, which was identified in 19 (34.5%) cases of mixed pulmonary infection. Human cytomegalovirus and Pneumocystis jirovecii, which were detected in 7 (12.7%) cases, were the most common co-pathogens in the group of mixed pulmonary infection. CONCLUSIONS mNGS is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity. TRIAL REGISTRATION (retrospectively registered): ChiCTR1900023727. Registrated 9 JUNE 2019.

中文翻译：

---

用于混合肺部感染诊断的超基因组下一代测序。

背景技术下一代基因组新一代测序（mNGS）作为病原体检测的一种有前途的技术正在兴起。然而，关于mNGS在混合性肺部感染中的应用的报道仍然很少。方法回顾性分析2018年7月至2019年3月的55例病例。根据初步诊断，将病例分为混合型肺部感染（36 [65.5％]）和非混合型肺部感染（19 [34.5％]）。比较了mNGS和常规检测在混合肺部感染诊断和病原体鉴定方面的表现。结果mNGS在混合型肺部感染诊断中的敏感性远高于常规检测（97.2％比13.9％； P <0.01），但特异性却相反（63.2％比94.7％； P = 0.07）。mNGS的阳性预测值为83.3％（95％CI，68.0-92.5％），阴性预测值为92.3％（95％CI，62.1-99.6％）。常规检测和mNGS鉴定共5例（9.1％）为混合肺部感染，但是，这两种方法的病原体鉴定结果在1例（1.8％）中是一致的。综上所述，mNGS检出的病原体3例（5.5％）与常规检测一致，混合肺部感染仅1例（1.8％）。根据我们的数据，与常规测试相比，mNGS在病原体检测方面具有更广的范围。特别地，mNGS的应用改善了肺部真菌感染的诊断。在55例病例中，mNGS在31例（56.4％）病例中检测到并鉴定出真菌，而常规测试中只有10例（18.2％）相同真菌呈阳性。在我们的研究中，通过mNGS检测到的最常见病原体是人巨细胞病毒，在19例（34.5％）混合肺部感染病例中被发现。在混合肺部感染组中，最常见的副致病菌是人巨细胞病毒和肺炎肺孢菌（7例，占12.7％）。结论mNGS是一种有前途的技术，可用于检测混合性肺部感染中的同病原体，具有提高速度和灵敏度的潜在优势。试用注册（追溯注册）：ChiCTR1900023727。注册于2019年6月9日。结论mNGS是一种有前途的技术，可用于检测混合性肺部感染中的同病原体，具有提高速度和灵敏度的潜在优势。试用注册（追溯注册）：ChiCTR1900023727。注册于2019年6月9日。结论mNGS是一种有前途的技术，可用于检测混合性肺部感染中的同病原体，具有提高速度和灵敏度的潜在优势。试用注册（追溯注册）：ChiCTR1900023727。注册于2019年6月9日。